Microbiota-liver axis in hepatic disease

Abstract

Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive proinflammatory gene expression, thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease.

Figure 1. Failure to maintain gut microbiota and its products in gut lumen may promote liver disease

A) A healthful microbiota is maintained in the gut lumen. B) Altered microbiota composition and/or altered barrier function can result in microbial products activating toll-like and nod-like receptors of the innate immune system. Such TLR/NLR activation can drive pro-inflammatory gene expression that promotes liver disease.

Figure 2. Potential therapeutic strategies to prevent or treat liver disease

1) Probiotics could maintain intestinal permeability by increasing the integrity of tight junctions or by preventing the overgrowth of harmful bacteria. 2) Prebiotics may act by improving the effect of probiotic bacteria or by impeding the growth of harmful bacteria. 3) Antibiotics could directly act by inhibition of harmful bacteria growth and 4) fecal transplant could lead to the restoration of a healthy microbiota. 5) Some therapeutics may act on the innate immune system by targeting TLRs signaling pathways or 6) NFκB inhibitors leading to lower expression of pro-inflammatory cytokine expression.